Refinement of the structure of Escherichia coli-derived rat intestinal fatty acid binding protein with bound oleate to 1.75-A resolution. Correlation with the structures of the apoprotein and the protein with bound palmitate.
Refinement of the structure of Escherichia coli-derived rat intestinal fatty acid binding protein with bound oleate to 1.75-A resolution. Correlation with the structures of the apoprotein and the protein with bound palmitate.
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DOI：
10.1016/s0021-9258(18)35872-1
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发表时间：
1992-11
期刊：
影响因子：
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通讯作者：
J. Sacchettini;G. Scapin;D. Gopaul;J. Gordon
中科院分区：
文献类型：
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作者：
J. Sacchettini;G. Scapin;D. Gopaul;J. Gordon
大鼠肠道脂肪酸结合蛋白（I-FABP）与结合油酸（C18:1）的结构已用x射线衍射数据细化到1.75 a的分辨率。该蛋白含有10条由99个残基组成的反平行β链和2条由14个残基组成的短螺旋。油酸位于蛋白质的内部，呈弯曲构象，C1-C12比C13-C18更有序。I-FABP：油酸酯中八个有序水中的两个是氢键网络的一部分，该网络包括油酸酯的羧酸盐、Arg106的胍基、Trp82的吲哚基的氮和Gln115的侧链。结合油酸酯的大部分亚甲基存在于疏水和芳香侧链形成的缝隙中。Tyr70和Tyr117包住了从C3到C8的酰基链，形成了van der Waals表面凹凸面的接触。每个酚侧链的羟基与有序的水分子成键。两种有序的水与结合脂肪酸的凹面发生范德华接触。油酸的-末端甲基是定向的，因此它指向Phe55的苯的中心，使它与它的组分亚甲基形成范德瓦尔斯相互作用。将I-FABP：油酸酯的结构与最近改进的1.19-A模型的apoI-FABP和早期的2.0-A模型的I-FABP：棕榈酸酯的结构进行比较，发现它们的主链和侧链原子的位置以及结合的油酸酯和棕榈酸酯的构象具有显著的相似性。主要的差异局限于蛋白质的几个离散区域。螺旋结构域，I型在β链C和D之间转，和Phe55的环一起形成了一个可通过溶剂进入蛋白质内部的门户。它们在I-FABP：油酸酯（和I-FABP：棕榈酸酯）中被重新定位，使结合腔更容易被溶剂接触，其体积也增加了。Phe55的侧链在载脂蛋白中表现出离散的紊乱，其功能是作为ω -末端的“传感装置”：随着结合脂肪酸的链长增加2个亚甲基，向表面逐渐向外移动。Tyr70和Tyr117在载脂蛋白结构上也表现出离散的紊乱，这是由于它们的C α -C β键周围的旋转，它们在全蛋白中稳定在一个单一的、有序的位置上。（摘要删节为400字）
The structure of rat intestinal fatty acid binding protein (I-FABP) with bound oleate (C18:1) has been refined with x-ray diffraction data to a resolution of 1.75 A. The protein contains 10 anti-parallel beta strands composed of 99 residues and 2 short helices of 14 residues. Oleate is located in the interior of the protein in a bent conformation with C1-C12 more ordered than C13-C18. Two of the eight ordered waters in I-FABP:oleate are part of a hydrogen bond network that includes the carboxylate of oleate, the guanidinium group of Arg106, the nitrogen of the indole group of Trp82, and the side chain of Gln115. Most of the methylenes of bound oleate reside in a crevice formed by hydrophobic and aromatic side chains. Tyr70 and Tyr117 envelop the acyl chain from C3 to C8 forming contacts with both the convex and concave faces of its van der Waals surface. The hydroxyls of each phenolic side chain hydrogen bond to ordered water molecules. Two ordered waters make van der Waals contact with the concave face of the bound fatty acid. The omega-terminal methyl of oleate is oriented so that it points toward the center of the benzene of Phe55 allowing it to form van der Waals interactions with its component methylenes. Comparison of the structure of I-FABP:oleate with a recently refined 1.19-A model of apoI-FABP and an earlier 2.0-A model of I-FABP:palmitate revealed a remarkable degree of similarity in the positions of their main chain and side chain atoms and in the conformations of the bound oleate and palmitate. The principal differences were confined to a few discrete regions of the protein. The helical domain, the type I turn between beta strands C and D, and the ring of Phe55 together form a solvent-accessible portal to the interior of the protein. They are repositioned in I-FABP:oleate (and I-FABP:palmitate) so that the binding cavity is even more accessible to solvent and its volume is increased. The side chain of Phe55 which shows discrete disorder in the apoprotein functions as an omega-terminal “sensing device”: moving progressively outward toward the surface as the chain length of the bound fatty acid increases by 2 methylenes. Tyr70 and Tyr117 which also show discrete disorder in the apoprotein structure due to rotation around their C alpha-C beta bonds, are stabilized in a single, well ordered position in the holoproteins.(ABSTRACT TRUNCATED AT 400 WORDS)